Rational combinations of radiation and chemotherapy which enhance tumor response and minimize normal tissue damage have not been derived clinically because of the lack of experimental data. The timing of chemotherapy relative to radiation is extremely important in this interaction and this timing is being studied at intervals from plus to minus 64 hours. Studies are being conducted in five normal tissue systems and five mouse model tum r systems as well as in vitro assays and in vivo cell lines from these systems. In addition, studies are evaluating the effects of drugs and drugs plus radiation on the immune system using immunocompetent T-cells. A limited number of human tumors carried in nude mice are also being evaluated with radiation and radiation plus cytoxic chemotherapeutic agents. The maximum effect as a function of time and drug dose will be compared for tumor and normal tissue and times of optimum therapeutic ratio derived.